DESCRIPTION (Investigator's Abstract): The broad, long-term objective of the proposed research is to provide more consistent and comparable models of traumatic brain injury (TBI) in the rat and mouse. Currently, it is difficult to precisely compare animal models across laboratories and optimize the settings in these models to study the distribution and severity of human closed head injury lesions. In this application, we use modeling and experimental tools to better quantitatively define and improve the biomechanics of small animal TBI models. The specific aims of the research are: Aim A: To determine the brain tissue deformations caused by three common rodent models of traumatic brain injury-weight - weight drop, controlled cortical impact, modified weight. Aim B: To determine the in vivo axonal, neuronal, and vascular tissue thresholds for mechanical injury in TBI models. Aim C: To rigorously determine the in vivo brain tissue deformation caused by the fluid percussion technique (lateral and midline) in the rat, developing biomedical measures that best predict mechanical injury. Aim D: To standardize a cortical impact model in the mouse that applies for a variety of mouse strains. By accomplishing the aims of the research plan, we expect to predict the mechanically-mediated damage caused by rat and mouse models of traumatic brain injury and establish precise parametric relationships to compare these models across laboratories. In addition, we expect to minimize the variability in new TBI models targeted to study traumatic brain injury sequelae in transgenically altered animals. Once accomplished, the research will significantly enhance existing models to understand the sequelae and treatment of human closed head injury.